Solid lipid nanoparticles of curcumin

Abstract

Provided herein is a process for preparing solid lipid nanoparticles of curcumin. Also provided herein are solid lipid nanoparticles of curcumin having a particle size in the range of 20-800 nm. The solid lipid nanoparticles of curcumin show a very high entrapment efficiency of curcumin in the range of 50-100% in terms of actual curcumin content of the formulation. The solid lipid nanoparticles of curcumin show increased efficacy of the curcumin.

The invention claimed is: 
     
         1 . Solid lipid nanoparticles of curcumin, comprising
 a. a lipid phase comprising of curcumin, lipid or mixture of lipids selected from group consisting of glycerides and fatty acids, and a co-solvent,
 wherein curcumin is entrapped in the lipid phase in a soluble/amorphous form; 
   b. an aqueous phase comprising water, curcumin, surfactant, and co-surfactant,
 wherein curcumin in the aqueous phase is in a solubilized form to prevent crystallization, 
   wherein the co-solvent is selected from polyethylene glycol, PVP, PVA, glycerol,-diethylene glycol monoethyl ether, glycerol monocaprylocaprate, polyethylene glycol monostearate, hydrogenated vegetable glycerides, glyceryl citrate, glyceryl lactate, glyceryl lincolate, glyceryl oleate, polyglyceryl-4-cocoate, polyglyceryl-3-carprate and derivatives thereof, polyglyceryl-3-capoylate and derivatives thereof.   
     
     
         2 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the solid lipid nanoparticles of curcumin have a particle size in the range of 20-800 nm. 
     
     
         3 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the solid lipid nanoparticles of curcumin have a spherical, ellipsoid, oblong, anisotropic, or rod shape. 
     
     
         4 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the solid lipid nanoparticles of curcumin increase the relative bioavailability of curcumin by 5 to 250 times with respect to free curcumin. 
     
     
         5 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the solid lipid nanoparticles show controlled release of curcumin up to 5 day or up to 9 days. 
     
     
         6 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the solid lipid nanoparticles offer photostability and protection to incorporated curcumin against pH degradation at pH 1.2, 6.8, 7.4, and 9 with increase in tin of curcumin by 2 to 20 times as compared to free curcumin. 
     
     
         7 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the solid lipid nanoparticles of curcumin show stability at 25° C. up to 6 months and 4° C. for more than one year. 
     
     
         8 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the aqueous solid lipid nanoparticles of curcumin are spray dried or lyophilised in 2 to 25% w/v of at least one of mannitol, trehalose, sucrose, lactose, and lactulose. 
     
     
         9 . The solid lipid nanoparticles of curcumin as claimed in  claim 1 , wherein the co-solvent is polyethylene glycol 600. 
     
     
         10 . A process for preparing solid lipid nanoparticles of curcumin of  claim 1 , the process comprising the steps of:
 a. dissolving curcumin in a co-solvent to obtain a solution and maintaining the solution at temperature 10° C. above lipid melting point temperature;   b. adding melted lipid or mixture of lipids selected from group consisting of glycerides and fatty acids to the solution obtained in step (a) to obtain a hot lipid phase;   c. preparing an aqueous surfactant phase comprising water, surfactant and co surfactant and maintaining the aqueous surfactant phase at a temperature 10° C. above lipid melting temperature;   d. adding the hot lipid phase of step (b) to the aqueous surfactant phase of step (c), or vice-versa, and mixing at high speed of 4000-15000 rpm for 5-10 min to obtain a primary coarse emulsion; and   e. subjecting the primary coarse emulsion of step (d) to two to six cycles of homogenization at 500 to 1200 bars to obtain solid lipid nanoparticles of curcumin.   
     
     
         11 . The process as claimed in  claim 10 , wherein the concentration of co-solvent in the solid lipid nanoparticle formulation is 5% to 8% w/w and the concentration of the surfactant in the solid lipid nanoparticle formulation is in the range of 8% to 12% w/w. 
     
     
         12 . The process as claimed in  claim 10 , wherein the mixture of the hot lipid phase of step (b) and the aqueous surfactant phase of step (c) is homogenized at 8000 rpm for 8 min to obtain a primary coarse emulsion. 
     
     
         13 . The process as claimed in  claim 10 , wherein step (e) comprises three cycles. 
     
     
         14 . The process as claimed in  claim 10 , wherein the glyceride is selected from the group consisting of glyceryl behenate tricaprin, trilaurin, trimyristin, tripalmitin, tristearin, 1,2-dioctanoyl-sn-glycerol, 1,2-didecanoyl-sn-glycerol, 1,2-dilauroyl-sn-glycerol, 1,2-dimyristoyl-sn-glycerol, 1,2-dipalmitoyl-sn-glycerol, 1-palmitoyl-2-oleoyl-sn-glycerol, 1-stearoyl-2-linoleoyl-sn-glycerol, 1-stearoyl-2-arachidonoyl-sn-glycerol, 1-stearoyl-2-docosahexaenoyl-sn-glycerol, 1-oleoyl-2-acetyl-sn-glycerol, 1,2-di-O-phytanyl-sn-glycerol, 1,2-dipalmitoyl ethylene glycol, 1-2-dioleoyl ethylene glycol, glyceryl monostearate, behenoyl polyoxyl-8 glycerides, glyceryl palmitostearate, 1-O-hexadecyl-sn-glycerol, 1-O-hexadecyl-2-acetyl-sn-glycerol, 1-O-hexadecyl-2-O-methyl-sn-glycerol, 1,2-diacyl-3-O-(α-D-glucopyranosyl)-sn-glycerol, stearoylmacrogol-32 glycerides, stearoyl polyoxyl-32 glycerides, lauroyl macrogol-32 glycerides, lauroyl polyoxyl-32 glycerides, lauroyl macrogol-6 glycerides, lauroylpolyoxyl-6 glycerides, oleoyl macrogol-6 glycerides, oleoyl polyoxyl-6 glycerides, linoleoyl macrogol-6 glycerides, polyglyceryl-3 dioleate, glycerol monolinoleate, glyceryl monolinoleate, glycerol monooleates, diethylene glycol monoethyl ether, glyceryl dibehenate, glycerol distearate, glyceryl distearate, glyceryl dipalmitostearate, linoleoyl polyoxyl-6 glyceride, behenyl alcohol, cetyl alcohol, and potassium cetyl alcohol. 
     
     
         15 . The process as claimed in  claim 10 , wherein the fatty acid is selected from the group consisting of saturated C4-C28 fatty acids and unsaturated C4-C28 fatty acids. 
     
     
         16 . The process as claimed in  claim 15 , wherein the fatty acid is stearic acid. 
     
     
         17 . The process as claimed in  claim 10 , wherein the surfactant is selected from the group consisting of ethylene oxide copolymers, propylene oxide copolymers, poloxamers, sorbitan ethylene oxide/propylene oxide copolymers, polysorbate 20, polysorbate 60, polysorbate 80, sorbitan esters, span 20, span 40, span 60, span 80, alkyllaryl polyether alcohol polymers, tyloxapol, bile salts, cholate, glycocholate, taurocholate, taurodeoxycholate, gemini surfactants, alcohols, diethylene glycol monoethyl ether, propanediol, capryl glucoside, decy glucoside, kolliwax, and mixtures thereof. 
     
     
         18 . The process as claimed in  claim 10 , wherein the co-surfactant is selected from the group consisting of soy lecithin, egg lecithin, phosphatidylcholine, cholate, glycocholate, taurocholate, taurodeoxycholate, and mixtures thereof. 
     
     
         19 . The process for preparing solid lipid nanoparticles of curcumin as claimed in  claim 10 , wherein curcumin content in the solid lipid nanoparticles is in the range of 0.5 to 10% w/v of the aqueous SLN dispersion and up to 50% w/w with respect to the lipid matrix. 
     
     
         20 . The process for preparing solid lipid nanoparticles of curcumin as claimed in  claim 10 , wherein entrapment efficiency of curcumin in the solid lipid nanoparticles is in the range of 50-100% in terms of actual curcumin content of the formulation.